GRP78 as potential predictor for breast cancer response to adjuvant taxane therapy

Int J Cancer. 2011 Feb 1;128(3):726-31. doi: 10.1002/ijc.25370.

Abstract

Few predictive markers exist for response to adjuvant chemotherapy in breast cancer. The 78-kDa glucose-regulated protein (GRP78) is a potent antiapoptotic factor, conferring drug resistance. Recently, we reported that high GRP78 expression in breast cancer specimens predicts a shorter recurrence-free survival in patients who received doxorubicin-based adjuvant chemotherapy. Interestingly, the opposite effect was observed in 25 patients who additionally received a taxane. To confirm this potentially paradigm shifting finding, we investigated whether GRP78 is associated with recurrence-free survival in an independent cohort of taxane-treated breast cancer patients. Immunohistochemical staining of GRP78 was performed on archival paraffin-embedded formalin-fixed tumor specimens obtained from 48 female breast cancer patients before chemotherapy treatment. These patients received doxorubicin and cyclophosphamide, followed by paclitaxel or docetaxel on a clinical trial. GRP78 expression level was evaluated by a pathologist, masked to all clinical and outcome data. Association between GRP78 expression and recurrence-free survival was evaluated. GRP78 positivity predicts a better recurrence-free survival, independent of other prognostic factors [hazard ratio (HR) for moderate positivity: 0.40 (95% confidence interval (CI): 0.087-1.83); HR for strong positivity: 0.16 (95% CI: 0.018-1.50); p(trend) = 0.053]. In a pooled analysis with the previous 25 patients, almost identical HRs were obtained with p(trend) = 0.024. This provides further evidence that GRP78 is a potential independent predictor for response to taxane-based adjuvant chemotherapy in breast cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Analysis of Variance
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers / analysis
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Cyclophosphamide / administration & dosage
  • Docetaxel
  • Doxorubicin / therapeutic use
  • Female
  • Heat-Shock Proteins / analysis
  • Heat-Shock Proteins / metabolism*
  • Humans
  • Lymphatic Metastasis
  • Menopause
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging
  • Paclitaxel / administration & dosage
  • Predictive Value of Tests
  • Taxoids / administration & dosage
  • Taxoids / therapeutic use*
  • Treatment Outcome

Substances

  • Biomarkers
  • Heat-Shock Proteins
  • Taxoids
  • Docetaxel
  • Doxorubicin
  • Cyclophosphamide
  • Paclitaxel
  • molecular chaperone GRP78